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International audience; Introduction: There is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients.Methods: The body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months.Results: The volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg.Conclusion: Fat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat.

Background and Purpose— The association of carotid atherosclerosis with body composition and fat distribution is poorly understood. We aimed to test the cross-sectional association of carotid plaques and common carotid artery intima-media thickness with calf circumference (CC), representing peripheral fat and lean mass, and with waist circumference and waist-to-hip ratio, 2 markers of abdominal obesity. Methods— The study was performed on 6265 subjects aged ≥65 years recruited prospectively from the electoral rolls of 3 French cities. Ultrasound examination and anthropometric measures were performed according to a standardized protocol. Results— Carotid plaques were less frequent with increasing CC, the ORs for the second, third, and fourth quartile of CC compared with the first quartile being 0.98 (95% CI, 0.84 to 1.15), 0.85 (95% CI, 0.72 to 1.01), and 0.71 (95% CI,:0.58 to 0.86; P for trend=0.0002), respectively, independently of age, gender, body mass index, and other vascular risk factors. There was an opposite and multiplicative effect of CC and waist-to-hip ratio on the frequency of carotid plaques (55.1% of individuals in the fourth waist-to-hip ratio quartile and the first CC quartile had carotid plaques, against 31.8% in the first waist-to-hip ratio and the fourth CC quartile). Mean common carotid artery intima-media thickness was larger with increasing waist circumference, waist-to-hip ratio, and CC, but the association with CC disappeared after adjusting for body mass index. Conclusion— The present study shows, for the first time, an inverse relationship between carotid plaques and CC. Although this needs to be confirmed in other populations, it may suggest an antiatherogenic effect of large CC.

Background The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (Methods We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Results Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4+ T-cell counts (≤200/mm3). Patients with low CD4+ T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4+ T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4+ T-cell count >500/mm3 as the reference), in addition to older age (P: +0.26 for a 10-year increase; P=0.01) and higher BMI (P: +0.07 for a 1-kg/m2 increase; P=0.003). Conclusions In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for altered insulin sensitivity.

Context: The endocannabinoid system modulates food intake and body weight in animal models. Treatment with the cannabinoid type 1 receptor blocker, rimonabant, reduces body weight in obese individuals. Objective: The aim of this study was to determine whether single nucleotide polymorphisms of the gene encoding cannabinoid type 1 receptor, CNR1, are associated with body fat mass and distribution in two independent samples of white European adult men. Design, Setting, and Participants: The 3813A/G and 4895A/G single nucleotide polymorphisms at the exon 4 of CNR1 were genotyped in 930 participants to the Olivetti Prospective Heart Study (OPHS) in Southern Italy and in 216 participants to the Wandsworth Heart and Stroke Study in the United Kingdom. Retrospective analysis was also performed on an OPHS subsample (n = 360) for which anthropometric data from 1987 and 1994–1995 examinations were available. Main Outcome Measures: CNR1 genotypes and anthropometric measures of body fat distribution were determined. Results: In the OPHS study, the 3813G allele was associated with increased subscapular skinfold thickness (24.2 ± 9.1 vs. 22.8 ± 7.7 mm; P = 0.031) and waist circumference (WC) (99.1 ± 8.8 vs. 97.7 ± 8.8 cm; P = 0.050). No association was observed with 4895A/G variant. Haplotype analysis confirmed that the unique haplotype carrying the 3813G was associated with increased WC and subscapular skinfold thickness. Similar results were observed in the OPHS retrospective subsample and the Wandsworth Heart and Stroke Study sample. In the latter, the 3813G was associated with increased WC (96.8 ± 11.3 vs. 91.6 ± 10.4 cm; P = 0.006). Conclusions: Genetic variants at CNR1 are associated with obesity-related phenotypes in men. The detection of polymorphic variants in genes involved in the process of fat accumulation may help identify specific targets for pharmacological treatment of obesity and related metabolic abnormalities.

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress., The authors conduct an in-depth analysis of a PGC-1β knockout mouse; these animals posses specific defects in basal mitochondrial function and adaptation to metabolic stress.